Penicillins derived from the reaction of enamines with 6-isocyanatopenicillanic acid saccharimide

ABSTRACT

NOVEL PENICILLANIC ACID DERIVATIVES HAVE BEEN PREPARED BY THE REACTION OF AN ENAMINE WITH 6-ISOCYANATOPENICILLANIC ACID SACCHARIMIDE.

United States Patent Olfice ABSTRACT OF THE DISCLOSURE Novel penicillanic acid derivatives have been prepared by the reaction of an enamine with 6-isocyanatopenicillanic acid saccharimide.

The invention is concerned with the production of novel penicillanic acid derivatives of Formula 1:

[CH3 f@ 0-: (H) \SO2 wherein R and R are (lower)alkyl; or R and R may be concatenated to form a heterocyclic ring selected from the group consisting of morpholino, piperidino, pyrrolidino, and N-alkylpiperazino; R and R are selected from the group consisting of hydrogen and (lower) alkyl; or R and R may be concatenated to form a ring selected from the group consisting of cyclopent-1-en-1,2-ylene, cyclohex- 1-ene-1,2-ylene, cyclohept-1-ene-1,2-ylene, 1-methyl-1,2,5, 6-tetrahydropyrid-3-ene-3,4-ylene.

As used herein the term (lower)alkyl is employed to describe hydrocarbon groups having one to about six carbon atoms such as methyl, ethyl, propyl, i-propyl, hexyl, etc. The term enamine is used to describe straight chain, branched chain, cyclic, substituted cyclic and fused ring structures containing the The novel enamine substituted penicillanic acid derivatives of the invention are prepared by reacting the appropriate enamine reactant with the saccharimide of 6-isocyanatopenicillanic acid. The reaction is conducted in an organic solvent such as dried methylene chloride tetrahydrofuran, chloroform, or any other appropriate solvent.

The following reaction scheme illustrates the process for the preparation of the compounds of the invention:

0 C N S CH3 T l l on: 03

\4. R\\ R3 R4 /NC=(-)H R2 R1 R3 R4 S CH N- :C-C-NH 3 7 01-13 s02 R2 0 N The novel enamine penicillanic acid saccharimides may be separated from the reaction mixture by in vacuo evap- 3,734,903 Patented May 22, 1973 oration of the solvent or by other techniques well known to those skilled in the art.

The novel compounds of the invention are antibacterial agents useful in treating bovine mastitis and other infections amenable to therapy with penicillanic acid derivatives such as benzylpenicillin. They are also useful as growth promoters for domestic animals such as cattle and hogs. The compounds of the invention are also useful for the inhibition of Staph. aureau, Smith at a concentration of less than micrograms/ml. when applied in an aqueous vehicle.

The following examples are added to illustrate but not to limit the scope of the invention:

EXAMPLE I 2-(6-[1,2,5,6-tetrahydro l methyl-4-(l-pyrrolidinyl) nicotinamido]-3,3-dimethyl 7 oxo-4-thia-1-azabicyclo[3.2.0]hept 2 ylcarbonyl)-l,2-benzisothiazolin-3- one 1,1-dioxide By methods analogous to those employed in Example I the following compounds are prepared:

3 We claim: attached, form a cyclic moiety selected from the group 1. A compound selected from the group consisting of: consisting of cyclopent-l-en-l, 2-ylcne, cyclohex-l-en-l, '2-ylene, cyclohept-l-en-l, 2-y1ene and 1-methy1-1,2,5, 3: 1 0 6-tetrahydropyrid-3-en-3,4-ylene. 1 l] s CH3 5 2. A compound as defined in claim 1 which is: 2-(6- i CNH CH3 CO [1,2,5,6-tetrahydro 1 methyl-4-(1-pyrr0lidinyl)nicotin- R, amido]-3,3-dimethyl-7-oxo 4 thia-1-azabicyclo[3.2.0] hept-Z-ylcarbonyl)-1,Z-benzisothiazolin-Ii-one 1,1-dioxide.

l (L 10 References Cited wherein UNITED STATES PATENTS R and R are individually (lower)alkyl and when taken 3,652,546 3/1972 Cheney et a1 260--239.1 together with the nitrogen atom to which they are at- 3,652,547 3/1972 Wolf et a1 260-2391 tached, form a heterocyclic ring selected from the group 3,652,548 3/1972 McCaully t a1, 260 239,1

consisting of piperidino, pyrrolidino, and N-(lower)al- 15 kylpiperazino; NICHOLAS S. RIZZO, Primary Examiner R and R are individually selected from the group consisting of hydrogen and (lower)alkyl and when taken U.S. Cl. X.R.

together with the cthenylene group to which they are 424-271 

